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Biomedical subjects

H Rühl

Publications and source records attributed to H Rühl.

At least 19 recordsLinked to original sources
PubMed1988

Atypical presentation of Hodgkin's disease in a patient at risk for the acquired immunodeficiency syndrome.

Hodgkin's disease (HD) has been reported in association with the acquired immunodeficiency syndrome (AIDS) only occasionally, and these patients seemed to have aggressive unusual HD. We report an additional case of HD in a 50-year-old homosexual man with a marked change of his clinical course after the development of seropositivity to human immunodeficiency virus (HIV). In 1978, HD stage IIIA, nodular sclerosing type, was diagnosed and treated with splenectomy and total nodal radiotherapy, which led to a complete response lasting till 1985. The patient then reported to our clinic with generalized lymphadenopathy and paresis of the m. biceps and m. triceps due to an infiltration of C6/C7 by HD. Laboratory findings revealed a T4/T8 ratio of 0.5 and HIV antibodies. He was given chemotherapy (COPP), but after a good initial response he developed pulmonary infiltration of HD. Therapy was changed to ABVD, but the patient did not respond to treatment and died of progressive HD in 1986. We therefore conclude that the natural history of HD in patients at risk for AIDS may be altered to a higher malignant form, and treatment modalities used in these patients must be further evaluated.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults.

In a prospective multicenter study, 368 acute lymphoblastic leukemia (ALL) patients aged 15 to 65 years were treated with an intensified induction and reinduction regimen; 272 (73.9%) achieved complete remission (CR). The median remission duration (MRD) is 24.3 months, and the probability of being in continuous CR (CCR) at greater than 5 years is .37. The median survival for all 368 patients is 27.5 months, and the probability of being alive at 5 years is .39. For the 272 patients in remission the median survival is 58.4 months, and the probability of being alive at 5 years is .49. A lower CR rate was seen for patients with bleeding at diagnosis or with splenomegaly/hepatosplenomegaly. The prognostic factors unfavorable for remission duration were time to CR greater than 4 weeks v less than 4 weeks (P = .0002), age greater than 35 years v less than 35 years (P = .0008), leukocyte count greater than 30,000/microL v less than 30,000/microL (P = .0112), and null ALL v common ALL (c-ALL)/T cell ALL (T-ALL) (P = .05). The remission duration correlated strongly (P = .0001) with the number of these independent prognostic factors. In patients with none of these adverse factors the MRD has not yet been reached, with one adverse factor the MRD is 21.9 months, and with two or three adverse factors the MRD is only 9.6 months. For the immunologic subtype T-ALL, the probability of being in CCR at greater than 5 years is .55; for c-ALL, .34; and for null ALL, .24. According to these results, patients were stratified into a low-risk group with a CCR rate of .62 and a high-risk group with a CCR rate of .28, with the latter now allocated to either further chemotherapy or bone marrow transplantation in first remission.

Adolescent↗
PubMed1985

Impaired B lymphocyte reactivity in patients after radiotherapy.

The effect of therapeutic irradiation upon B lymphocyte function was investigated in patients with various malignancies. The test system used was a reverse hemolytic plaque assay, which made it possible to study the activation and differentiation of B lymphocytes into immunoglobulin-secreting cells (ISC). Peripheral blood lymphocytes from normal individuals and patients before and after radiotherapy were stimulated in vitro with the polyclonal B cell activator pokeweed mitogen, and the number of ISC was estimated. B cell reactivity was markedly reduced in those patients who had received irradiation within the last six months. In patients in whom radiotherapy had been terminated more than 12 months before the lymphocytes were tested, B cell reactivity was comparable to that of patients prior to radiotherapy. By means of marker analyses, there was a reduction of B lymphocytes and T lymphocytes in the peripheral blood with a preponderance of T helper cells. Several mechanisms--e.g., reduced or defective B cell differentiation, altered regulatory T-helper or suppressor cell function or activation of suppressive monocytes--could be responsible for impaired B cell reactivity after radiotherapy.

Adult↗
PubMed1985

Abnormalities of B-cell activation and immunoregulation in splenectomized patients.

Using a reverse hemolytic plaque assay as the effector system, we studied B-lymphocyte function in 12 patients after posttraumatic splenectomy, as well as in 25 normal individuals. The time interval between the splenectomy and the immunological studies varied between 2 days and 7 years. Compared to normal individuals, the splenectomized patients had markedly elevated numbers of spontaneous immunoglobulin-secreting cells (ISC) and severely decreased responses to the polyclonal activator pokeweed mitogen. A tendency towards normalization of these abnormalities, especially the high spontaneous ISC levels, could be observed during the time interval extending up to 7 years after splenectomy. In order to characterize the mechanism responsible for the altered immune response in splenectomized patients, co-culture experiments with unseparated and separated lymphocytes were performed. These revealed an impaired T-helper cell capacity as well as an intrinsic B-cell defect. Marker analyses with monoclonal antibodies revealed normal proportions with the exception of OKT 4 positive and B 1 positive cells that identify T-helper/inducer and peripheral B-cells respectively. We conclude that immune dysfunction in peripheral blood lymphocytes of splenectomized patients involves mainly the B-cell as well as the T-helper/inducer-cell population.

Adult↗
PubMed1985

Chronic lymphocytic leukemia B-lymphocytes forming SRBC-rosettes not due to an anti-SRBC activity of monoclonal surface immunoglobulin.

A case of chronic lymphocytic leukemia is described in which large numbers of peripheral blood lymphocytes expressed immunoglobulin on their membrane and rosetted spontaneously with sheep red blood cells (SRBC) at 4 degrees C. They also showed weak staining with a heterologous antiserum against T-cells as well as with a monoclonal antibody (OKT11) with specificity for an epitope associated with the SRBC-receptor, but failed to react with other T-lineage-restricted monoclonal antibodies. The B-cell origin of the leukemic cells was documented by the presence of light-chain-restricted monoclonal surface immunoglobulin, reactivity with various monoclonal anti-B-cell reagents, presence of Ia-like antigens, their capability to synthesize intracytoplasmic immunoglobulin on exposure to phorbol ester TPA, their lack of response to T-cell mitogen PHA, and their inability to help or suppress the allogeneic B-cell response upon PWM stimulation. Extensive blocking studies with both specific antisera and Forsmann antigen-rich guinea pig kidney extracts, which did not prevent SRBC-rosetting, lend support to the hypothesis that SRBC-rosette formation in this case was not attributable to an anti-SRBC affinity of the surface immunoglobulin on the cells. This case will be discussed in relation to the recent finding of SRBC-rosette expression on some cultured chronic lymphocytic leukemia B-lymphocytes.

Aged↗
PubMed1985

Intensified induction and consolidation with or without maintenance chemotherapy for acute myeloid leukemia (AML): two multicenter studies of the German AML Cooperative Group.

In two multicenter trials, a total of 576 patients with acute myeloid leukemia (AML) were treated and found to be evaluable. Two hundred forty-two patients were in a 1978 pilot study and 334 patients were in a 1982 randomized study. Ages were between 15 and 78 years (median, 48). The uniform remission induction therapy in both studies consisted of one to two courses of a 9-day combination of 6-thioguanine (TG) with cytosine arabinoside (ARA-C) and daunorubicin (DNR) [TAD9]. The timing and sequencing of TAD9 was designed according to cell kinetic effects of ARA-C. A complete remission (CR) was achieved in 65% (70% and 61%, respectively) of patients within a median of 33 days, and in 68% of responders after only one course. The CR rate in patients 60 to 78 years of age was 51% (66% and 39%, respectively). In the 1978 pilot study, different protocols of post-remission treatment were applied at the different centers: monthly 5-day maintenance, TAD9 consolidation, both consolidation and maintenance, or no further therapy. The group receiving treatment during CR showed 24% probability of remissions at 4 years v 0% probability of remissions in the untreated group. Between the different post-remission protocols, no significant differences were observed. Remission duration was not influenced by age, WBC, or morphologic cell type, but was longer in patients achieving CR within 30 days (P = .017). In the subsequent 1982 study, 145 patients in CR were randomized for TAD9 consolidation with or without monthly maintenance. The updated life-table analysis revealed a predicted rate of continuous remission at 2 1/2 years of 30% for the maintenance and 17% for the nonmaintenance arm (P = .003). These results of response and remission duration in adult patients of all ages support the validity of intensified induction therapy and of consequent myelosuppressive treatment in remission.

Actuarial Analysis↗
PubMed1985

[Characterization of the leukemic cell population in a patient with T-ALL at disease beginning and in recurrence: parallel changes in phenotypic and functional behavior].

The phenotypic and functional characteristics of the leukemic cells from one patient with a suppressor T-ALL were studied. At the time of diagnosis a high proportion of OKT8 positive (suppressor/cytotoxic) cells were identified which mediated strong suppressor activity to the differentiation of allogenic B-cells. A complete remission of 12 months duration was achieved by chemotherapy. In the relapse the marker analysis showed a dramatic decrease of the OKT8 positive cell fraction. Functionally the suppressor activity was completely lost indicating a close correlation between phenotype and functional activity also in a leukemic cell population.

Adult↗
PubMed1985

Coincident change of cellular function and phenotype in the course of a suppressor T cell acute lymphocytic leukaemia.

The phenotypic and functional characteristics of the leukaemic cells from one patient with T suppressor ALL were studied at the time of diagnosis and in relapse. At the time of diagnosis, the phenotype corresponded to the intermediate stage between the cortical and medullary phases of normal thymocyte differentiation with a high proportion of T8+ cells (E-R+, TdT+, C3bR-, T3-, T4-, T6+, T8++, T10+). Functionally, the cells did not respond to mitogens but mediated strong suppressor activity to allogeneic B-cells, as measured in a reversely haemolytic plaque test. Clinically, the patient exhibited the uncommon feature of hypogammaglobulinaemia. Induction therapy led to complete remission, which continued for 12 months. In the relapse, the phenotype remained essentially stable except for a dramatic decrease of the T8+ cell fraction and an increase of the T10+ cell fraction. Functionally, the suppressor activity was completely lost, indicating a close correlation between phenotype and functional activity in this leukaemic cell population.

Adult↗
PubMed1979

Activation of human lymphocyte subpopulations by protein A from Staphylococcus aureus bacteria.

Cowan I strain Staphylococcus aureus bacteria were found to be mitogenic for human peripheral and cord blood lymphocytes. Experiments with lymphocyte supopulations otained by nylon wool filtration and/or E-rosette separation revealed that T-lymphocytes are the main target cells, whereas isolated B cells did not respond significantly. Further experiments suggested that B cells could be activated in the presence of mitomycin-treated T cells. Null cell-enriched lymphocyte suspensions could be stimulated by Con A but not by the bacteria or by PHA.

B-Lymphocytes↗
PubMed1979

Zinc metabolism in normal, lectin-stimulated and leukemic lymphocytes.

Gel filtration of the cytoplasmic fraction of homogenate from human peripheral lymphocytes incubated with 65Zn gave five separate peaks with molecular weights of greater than 150,000, 90,000, 65,000, 20,000, and less than 1000 daltons. Peaks I--IV consisted of proteins. The low molecular weight (peak V) may consist of nucleotides, polyamines and amino acids. After gel filtration 75-80% of the 65Zn activity was found in peak V. Lectin-induced stimulation of normal lymphocytes revealed a distribution pattern of 65Zn binding similar to that of unstimulated cells. There was only a slightly enhanced incorporation into the protein peaks I--IV. When peripheral lymphocytes of B lymphocyte origin from patients with chronic lymphocytic leukemia were incubated with 65Zn the same peaks were seen as with supernatants obtained from normal lymphocytes. Lectin-induced stimulation of leukemic lymphocytes had no significant effect on the 65Zn distribution pattern.

Carrier Proteins↗
PubMed1978

Activation of lymphocyte subpopulations in patients with chronic lymphocytic leukemia.

T lymphocytes from the peripheral blood of normal donors and patients with CLL were isolated by nylon wool filtration or E-rosette separation and tested for functional activities. Unseparated CLL lymphocytes showed a poor response to phytomitogens and to allogeneic cells. Subpopulations enriched in E-RFC showed an increased PHA- and a normal MLC-reactivity; the Con A responses, however, were markedly reduced in all experiments. Subpopulations which were T cell depleted showed no reactivity to all mitogens. Purified T cells from normal donors showed a decreased reactivity to PHA, Con A and PWM. The Con A responses were completely abolished in almost all experiments. These diminished responses could be restored by unseparated cells or by small numbers of syngeneic, mitomycin-treated monocytes. The data suggest that mitogen-induced T lymphocyte stimulation in vitro in general depends on the presence of monocytes.

Antibody-Producing Cells↗